Considerable data suggest that the polymerization of pentamer IgM antibodies is an integral step in the initiation and control of the immune response. In precursors of antibody-synthesizing cells, the binding of antigen to surface monomeric IgM signals an increased synthesis of the monomers and their assembly and secretion as 19S polymers. The 19S product in turn appears to exert positive feedback and signal a switchover from polymer IgM to monomer IgG synthesis. These signalling processes will be investigated by use of the following approaches: 1. Since J chain is an essential component of pentameric, but not monomeric IgM, its synthesis and the subsequent IgM polymerization will be followed in mitogen stimulated human and rabbit B lymphocytes. Other intermediates of the activation pathway will be investigated by use of inhibitors of RNA synthesis, protein synthesis, and immunoglobulin secretion. 2. Positive regulation by 19S IgM is presumably exerted after combination with specific antigen. Antigen induced conformational changes will be studied in anti-hapten rabbit IgM and the activated IgM complexes will be assayed for their interaction with surface receptors on B cells, T cells, and macrophages. 3. The relationship between the genes controlling J and heavy chain synthesis will be explored by a) attempting to identify J chain allotypes in the rabbit and thus permit linkage determinations and b) correlating the expression of J chain genes with the expression of heavy chain genes in plasma cells and memory cells.